1. Field of the Invention
Embodiments of the invention are in the field of analyte sensors, more particularly, micro- or nano-electro-mechanical (MEMS; NEMS) resonator-based sensors and, most particularly, MEMS/NEMS, statically-buckled resonator-based sensors, methods of making, and applications thereof.
2. Related Art
A need exists for fast and inexpensive trace vapor detectors. Microsensors based on electrochemical, surface acoustic wave, optical, and mechanical transduction are under investigation to meet this demand. Sensors based on microelectromechanical systems (MEMS) are candidates for a wide range of sensing applications including environmental monitoring; biological, biomedical and biochemical analysis; health monitoring; and detection of explosives for security use and landmine sweeping.
Microcantilevers have been the primary MEMS structures used in sensors research. FIGS. 1A, 1B schematically illustrate, respectively, a MEMS cantilever with a reactive coating on multiple sides corresponding to a resonant mode and, on a single side corresponding to a deflection mode. Changes in the resonance frequency of the cantilever due to the added mass of analyte or changes in materials properties due to chemical interaction between the analyte and a reactive coating are measured using these devices. Gravimetric mass sensors have proven extremely sensitive in vacuum. Various surface coatings and treatments have been developed for use at ambient pressure where sensitivity is lower due to viscous losses. Alternately, cantilevers are coated on a single side with a reactive layer that swells or contracts upon contact with an analyte and a static deflection is measured. In functionalized cantilever studies, deflection of the composite structure relieves the stress induced by these volumetric changes.
Breath gas analysis is a well documented technology that uses a variety of techniques spanning the scale from proton-transfer-reaction mass spectrometry and ion-molecule-reaction mass spectrometry, to the deflection of cantilevers. The prospect of directly analyzing ‘breath gas’ for various volatile organic compounds (VOCs) raises the possibility of monitoring human performance and stress, as well as enabling a broad-based non-invasive tool for diagnosis and monitoring.
Breath gas components acetaldehyde, acetone, ethanol, isoprene have been monitored, with isoprene in particular correlated to heart rate. Acetaldehyde, an oxidation product of ethanol, is seen to decrease during sleep, while isoprene is related to the biosynthesis of cholesterol and shows a time variation during sleep correlated to heart rate. Other gasses, e.g., o-toluidine, show correlation to lung carcinoma. Thus it is well established that by measuring various volatile organic compounds, important physiological information can be obtained from the breath of human subjects. The typical range of relevant gas concentrations are 100s to 1000s of ppb.
Prior technology pioneered the use of the time dependent deflection of a cantilever array on which a variety of polymer coatings were deposited to resolve the presence of VOCs using principal component analysis (a ‘NOSE’). The analysis also demonstrated success in resolving signatures from various alcohols (from heptanol to methanol), as well as acetone, toluene, dichloromethane and heptane. Response times were relatively rapid (on the order of a few seconds). The ‘NOSE’ was used to carry out a neural network analysis of various natural flavors (M. K. Baller, H. P. Lang, J. Fritz, Ch. Gerber, J. K. Gimzewski, U. Drechsler, H. Rothuizen, M. Despont, F. M. Battiston, J. P. Ramseyer, P. Formaro, E. Meyer, J. J. Guntehrrodt, “A cantilever array-based artificial nose”, Ultramicroscopy 82 1-9 (2000)).
FIGS. 2(a-d) show data published by the same group on the response of a cantilever array to breath gas from two healthy patients (a, b) and two patients with renal disease (uraemia) (c, d). A compound found in patient's breath associated with uraemia is dimethylamine, which is presumably the sensed VOC. It is noted that the detection response time in the 100s of seconds (H. P. Lang, J. P. Ramseyer, W. Grange, T. Braun, D. Schmid, P. Hunziker, C. Jung, M. Hegner, C. Gerber “An Artificial Nose Based on Microcantilever Array Sensors”, Journal of Physics: Conference Series 61 (2007) 663-667 doi:10.1088/1742-6596/61/1/133 International Conference on Nanoscience and Technology (ICN&T 2006)).
Other studies have compared resonant frequency shifts and cantilever deflection as a methodology for signal extraction. The VOC sensed was RDX vapor on a carboxyl-terminated self-assembled mono-layer (SAM) of 4-mercaptobenzoic acid (4-MBA aka thiosalicylic acid) (Thomas Thundat, Lal Pinnaduwage and Richard Lareau, “Explosive Vapour Detection using micromechanical sensors” in Electronic Noses & Sensors for the Detection of explosives, 249-266, J. W. Gardner and J. Yimon, eds. Kluwer (Netherlands) (2004)). FIG. 3 (their result) shows negligible sensitivity of the resonant frequency to RDX vapor in contrast to the robust signal from deflection. The deflection of the cantilever is attributed to stress in the SAM that induces bending in the cantilever. The same group also demonstrated mass absorption induced frequency shift at the 15 pg level of PETN on their 4-MBA functionalized cantilever; resolution was estimated at the few pg level.
Resonant cantilevers were used without functionalization to demonstrate sensitivity to ethanol (S-J. Kim, T Ono, M. Esashi, “Mass detection using capacitive resonant silicon resonator employing LC resonant technique” Rev. Sci. Instr., 78 085103-1-6 (2007)). In that study, the researchers hypothesized that the increase in resonant frequency observed (100 Hz shift compared to 81 kHz frequency) with a Q=10 in ambient air when the cantilever was exposed to moisture in the air was due to a change in stress in the native oxide layer on the cantilever's surface. In contrast, exposure to ethanol laden air evoked a negative frequency shift due to adsorption of the ethanol vapor. The concentrations of analytes were 1400 ppm (water) and unknown for the ethanol.
Cantilever deflection by exposure to DNT via diffusion of the VOC into a nano-porous material, TBC6A (thickness 300 to 500 nm) has also been demonstrated (P. G. Datskos, N. V. Lavrik, and M. J. Sepaniak, “Detection of Explosive Compounds with the Use of Microcantilevers with Nanoporous Coatings”, Sensor Letters, 1, 25-32, (2003)). In that study, a μm thick coating of TBC6A was deposited by thermal evaporation on a cantilever. The cantilevers were able to resolve the presence of TNT and its various derivatives. However, the response time was excessively long, though the researchers were able to demonstrate improvement in the response time by elevating the temperature of the substrate.
The same group demonstrated a true “nose” similar to the Baller et al. work referred to above by thermally evaporating various organic compounds on nanostructured gold surfaces. They demonstrated a deflection response to a variety of VOCs from CO2 to tri- and tetra-chlorethylene via nine different coatings thermally evaporated onto a cantilever array. The responses were examined with an artificial neural network (ANN) algorithm, enabling identification of individual components as well as the ability to assay them from a mixture (P. G. Datskos, N. V. Lavrik, M. J. Sepaniak, and P. Dutta, “Chemical sensors based on functionalized microcantilever arrays”, IEEE sensors Exco Korea Oct 22 862-867, (2006) and C. A. Tipple, N. V. Lavrik, M. Cuha, J. Headrick, P. Datskos, and M. J. Sepaniak, “Nanostructured Microcantilevers with functionalized cyclodextrin receptor phases: Self assembled monolayers and vapor deposited films”, Anal. Chem., 74, 3118-3126 (2004)).
The methodology of ANN or Principal Component Analysis (PCA) is similar to that employed in commercial handheld noses that rely on mass adsorption and resonant frequency shift of quartz crystal microbalances (Quartz Crystal Monitors-QCMs). Though the various coatings of the QCMs are proprietary, it is hypothesized that as long as there is a differential response to various analytes, coatings can be relatively simple. It is clear that the distinguishing feature of the QCM vs. cantilever responses in terms of the resonant frequency shift is the fact that cantilevers are highly dissipative in air, thus relinquishing their surface area/volume advantage over QCMs, which have relatively high Qs in ambient air at the expense of poor surface/volume. Most commercial handheld noses use four to eight sensors, cost between 10000 and 25000 USD, and require battery power that is limited to a few hours of operation.
In view of the foregoing discussion as well as other information known in the art, the inventors have recognized the benefits and advantages that would be provided over cantilever-based sensors, QCMs used in current VOC monitors, and lab-based gas chromatography by sensor apparatus and methods that operate more rapidly (seconds vs. minutes) due to reduced thickness of the functionalizing film, especially for nano-porous materials, and comparable to the time constant of delivery of the gas to the sensor; that ease the readout of the sensor (e.g., frequency rather than deflection, with no requirement for the large dimensions needed for the optical measurement of deflection). That can provide a miniaturized array of sensors on a chip scale; that have reduced cost, size, and power requirements; and others. Besides medical applications, such devices could also find utility in a variety of consumer applications from food packaging to cosmetics, and defense applications ranging from explosives detection to munitions monitoring.